The mono-oxygenase activity in vitro towards 7-ethoxyresorufin (ERR) and 2,5-diphenyloxazole (PPO) was studied in 108 human placental homogenates obtained from mothers who were either smokers (61), non-smokers (44), or epileptics (3). With both substrates the average placental AHH level among smokers was 50 to 60 times greater than the average level in nonsmokers. Some association was found between levels of placental AHH activity and the number of cigarettes smoked per day by the woman concerned: PPO, r = 0.42, P less than 0.01; ERR, r = 0.39, P less than 0.01. In smokers, placental PPO hydroxylase and ERR O-deethylase activities were highly significantly correlated (r = 0.96, P less than 0.001). In non-smokers the low average levels of AHH activity obtained using both substrates were found to be significantly non-zero: PPO, P less than 0.01; ERR, P less than 0.001. No correlation was found, in either smokers or non-smokers, between placental AHH activity and parameters such as age, body weight, diet (including consumption of tea, coffee and alcohol), number of previous pregnancies or placental and baby birth weights. Women who continued smoking during pregnancy but at a reduced rate still maintained fairly high levels of AHH activity. Administration of carbamazepine appeared to cause some enhancement of placental AHH activity. Phenytoin administration, however, had no apparent effect on the level of enzyme activity.